Ferroptosis and its potential as a therapeutic target

Biochem Pharmacol. 2021 Apr:186:114486. doi: 10.1016/j.bcp.2021.114486. Epub 2021 Feb 23.

Abstract

Ferroptosis is a recently defined form of programmed cell death that is different from apoptosis. It is an iron-dependent programmed cell death and the accumulation of lipid hydroperoxides to lethal levels make ferroptosis distinct. Ferroptosis can be effectively regulated by a number of cellular variables including iron content, amino acid uptake, polyunsaturated fatty acid incorporation, glutathione biosynthesis, and NADPH levels. A number of severe and common degenerative diseases in humans such as Parkinson's disease and Huntington's disease, as well as several acute injury scenarios, such as stroke, intracerebral hemorrhage, traumatic brain injury, and ischemia-reperfusion injury are likely to be linked to ferroptosis. Ferroptosis may play a critical role in tumor-suppression and has been proposed as a potential target for cancer therapy. However, regulating ferroptosis in vivo remains difficult due to a lack of compounds that can effectively activate or repress ferroptosis. Here we review the cellular mechanisms underlying ferroptosis and the pathophysiological circumstances where its regulation could be beneficial.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cerebrovascular Disorders / drug therapy
  • Cerebrovascular Disorders / metabolism
  • Drug Delivery Systems / methods*
  • Ferroptosis / drug effects*
  • Ferroptosis / physiology*
  • Humans
  • Lipid Peroxidation / drug effects*
  • Lipid Peroxidation / physiology*
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / metabolism
  • Neuroprotective Agents / administration & dosage
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Neuroprotective Agents
  • Reactive Oxygen Species